Meditation as a bioactive intervention: evidence of translational potential via Connectivity Mapping and TMS neurophysiology

Background: Meditation practices are often used as non-pharmacological adjunct therapy for managing stress and wellbeing benefits. Here, we investigate whether molecular signatures via meditation practices have potential overlap with those of known drug targets that have established neurophysiological relevance.

Method: We leverage the Connectivity Map (CMap) to investigate (a) the overlap between meditation-induced molecular signatures and established drug responses, and (b) the pathways and mechanisms contributing to meditation’s potential therapeutic effects. This was studied in a comprehensive temporal RNAseq dataset comprising premeditation, meditation, and follow-up stages from a clinical trial involving 106 participants practizing inner engineering meditation. With Multiple Correspondence Analysis (MCA), we then examined how overlapping neuroactive drug classes identified from a systematic-literature search derived pharmaco-Transcranial Magnetic Stimulation (TMS) responses and CMap results co-occurred within a shared latent space.

Results: Meditation associated signatures overlapped with over 438 drugs, but predominantly with drugs targeting the neuroactive ligand interaction receptor pathways, capable of modulating the brain’s excitation-inhibition (E/I) balance. We found that meditation associated transcriptome signatures showed connectivity with drugs targeting the GABA, glutamine and other neuromodulatory system pathways. This pattern was further corroborated by Multiple Correspondence Analysis (MCA) of drugs from pharmaco-TMS studies and CMap, which revealed distinct temporal patterns of these drug classes across meditation stages.

Conclusion: This integrative approach offers a molecular lens to view meditation’s potential neurophysiological effects. Rather than establishing causal mechanisms, our findings are intended to generate hypotheses: how meditation-associated molecular pathway changes might relate to shifts in E/I balance. We propose a working model to test these associations directly using neurophysiological measures, with the eventual goal of informing evidence-based clinical applications. Overall, these exploratory findings have increased the potential possibility to correlate meditation with biologically relevant molecular and neurophysiological correlates, hence, providing an additional dimension to meditation’s currently established characterization as a psychological and contemplative practice.